Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing

Abstract

How different organs in the body sense growth perturbations in distant tissues to coordinate their size during development is poorly understood. Here, we mutated an invertebrate orphan relaxin receptor, the Drosophila Lgr3, and found body asymmetries similar to those found in insulin/relaxin-like peptide 8 (dilp8) mutants, which fail to coordinate growth with developmental timing. Indeed, mutation or RNAi against Lgr3 suppresses the delay in pupariation induced by imaginal disc growth perturbation or ectopic Dilp8 expression. By fluorescently-tagging the endogenous Lgr3 protein and performing CNS-specific RNAi, we find that Lgr3 is expressed and required in a novel subset of CNS neurons to transmit the peripheral tissue stress signal, Dilp8, to the neuroendocrine centers controlling developmental timing. Our work sheds new light on the function and evolution of relaxin receptors and reveals a novel neuroendocrine circuit responsive to growth aberrations.